423 Long-term efficacy of abrocitinib up to 96 weeks in adults with moderate-to-severe atopic dermatitis stratified by age: a post hoc analysis of the JADE EXTEND phase 3 trial
Authors: Andrew F Alexis, Mette Deleuran, Jonathan I   Silverberg, Melinda J Gooderham, Saleem A Farooqui, Gary Chan, Herwig  Koppensteiner, Pinaki Biswas, Melissa Watkins
Journal: British Journal of Dermatology (2023)

Abstract Oral abrocitinib 200 and 100 mg once daily provided short-term efficacy in a dose-dependent manner over 12 or 16 weeks in various age groups of patients with moderate-to-severe atopic dermatitis (AD). This study aims to evaluate the long-term efficacy of abrocitinib treatment for up to 96 weeks in adult patients with moderate-to-severe AD who enrolled in JADE EXTEND (NCT03422822). This planned interim analysis included adult patients from the JADE clinical trials MONO-1 (NCT03349060), MONO-2 (NCT03575871), COMPARE (NCT03720470) and DARE (NCT04345367) who subsequently enrolled into the ongoing phase 3 extension trial JADE EXTEND (data cutoff: September 25, 2021). Patients who were randomly assigned to abrocitinib 200 or 100 mg once daily in the qualifying trials continued to receive the same dose in JADE EXTEND with blinding maintained; those who received placebo were randomly assigned to abrocitinib 200 or 100 mg. All patients from JADE DARE received a known dose of abrocitinib 200 mg in JADE EXTEND. Patients previously randomly assigned to dupilumab in JADE DARE or JADE COMPARE were excluded from this analysis. Patients were grouped for analysis by age (18–50 years; &amp;gt;50 years) recorded at the screening visit of the respective qualifying trial. Assessments included the proportion of patients who achieved Investigator’s Global Assessment (IGA) score of 0 (clear) or 1 (almost clear) with a ≥2-grade improvement from baseline, ≥75% and ≥90% improvement from baseline on the Eczema Area and Severity Index (EASI-75 and EASI-90), a score of &amp;lt;2 or a ≥4-point improvement from baseline in Peak Pruritus Numerical Rating Scale score (PP-NRS 0/1 or PP-NRS4), and a score of &amp;lt;2 on the Dermatology Life Quality Index (DLQI 0/1). Data (as observed values) were evaluated up to 96 weeks of abrocitinib treatment. A total of 1309 patients [18–50 years (n = 1046); &amp;gt;50 years (n = 263)] were analysed. At Week 16 of abrocitinib treatment, patients achieved improvements with abrocitinib 200 or 100 mg in a dose-dependent manner in both age groups for IGA 0/1 [18–50 years, 55% (abrocitinib 200 mg)/34% (abrocitinib 100 mg); &amp;gt;50 years, 56%/38%], EASI-75 (79%/61%; 76%/69%) and PP-NRS4 (70%/51%; 76%/61%). Similar dose-dependent responses in both age groups were observed for the high-threshold clinical, patient-reported and health-related quality of life (HRQoL) endpoints of EASI-90 [18–50 years, 54% (abrocitinib 200 mg)/33% (abrocitinib 100 mg); &amp;gt;50 years, 59%/40%], PP-NRS 0/1 (35%/25%; 54%/30%) and DLQI 0/1 (38%/23%; 47%/24%). Regardless of age and dose, substantial proportions of patients were observed with responses at Weeks 24, 48 and 96 of abrocitinib treatment. At Week 96, dose-dependent responses remained for the younger subgroup of patients (including for high-threshold responses). For the older subgroup, responses were less clearly dose-dependent from Week 48. At Week 96, responder proportions were as follows: for IGA 0/1: 18–50 years, 55% (abrocitinib 200 mg)/44% (abrocitinib 100 mg); &amp;gt;50 years, 58%/51%; for EASI-75: 85%/73%, 89%/86%; for PP-NRS4: 66%/54%; 80%/79%; and for the high-threshold endpoints of EASI-90: 58%/45%; 73%/58%; for PP-NRS 0/1: 38%/26%; 44%/54%; and for DLQI 0/1: 41%/32%; 48%/51%. Regardless of age, substantial proportions of adults achieved clinical and patient-reported endpoints (IGA 0/1, EASI-75 or PP-NRS4) after short-term treatment with either abrocitinib dose. Similar trends were observed for high-threshold clinical, patient-reported and HRQoL endpoints (EASI-90, PP-NRS 0/1 or DLQI 0/1). Dose-dependent efficacy was observed short-term regardless of age, and up to 96 weeks in patients aged 18–50 years. Responder proportions of patients aged &amp;gt;50 years were less clearly dose-dependent from Week 48 of abrocitinib treatment. These findings may be informative for patients and healthcare providers when making treatment decisions. Further data from the ongoing JADE EXTEND trial may provide greater precision for long-term efficacy estimates.